rs6668814

Positions:

• chr1-111242504-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004000.3(CHI3L2):​c.*2+138C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.097 in 875,548 control chromosomes in the GnomAD database, including 6,074 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.090 (951 hom., cov: 32)
  • Exomes 𝑓: 0.099 (5123 hom.)
• Consequence: CHI3L2 NM_004000.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.41

Genes affected

CHI3L2 (HGNC:1933): (chitinase 3 like 2) The protein encoded by this gene is similar to bacterial chitinases but lacks chitinase activity. The encoded protein is secreted and is involved in cartilage biogenesis. Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Apr 2012]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.342 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CHI3L2	NM_004000.3	c.*2+138C>T		intron_variant		ENST00000369748.9
CHI3L2	NM_001025197.1	c.*2+138C>T		intron_variant
CHI3L2	NM_001025199.2	c.*2+138C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CHI3L2	ENST00000369748.9	c.*2+138C>T		intron_variant		1	NM_004000.3	P1

Frequencies

GnomAD3 genomes AF: 0.0898 AC: 13649 AN: 152050 Hom.: 958 Cov.: 32

Gnomad AFR AF: 0.0325

Gnomad AMI AF: 0.0603

Gnomad AMR AF: 0.102

Gnomad ASJ AF: 0.0418

Gnomad EAS AF: 0.357

Gnomad SAS AF: 0.185

Gnomad FIN AF: 0.176

Gnomad MID AF: 0.0222

Gnomad NFE AF: 0.0848

Gnomad OTH AF: 0.0794

GnomAD4 exome AF: 0.0986 AC: 71295 AN: 723380 Hom.: 5123 Cov.: 10 AF XY: 0.0991 AC XY: 35778 AN XY: 361124

Gnomad4 AFR exome AF: 0.0276

Gnomad4 AMR exome AF: 0.0936

Gnomad4 ASJ exome AF: 0.0388

Gnomad4 EAS exome AF: 0.365

Gnomad4 SAS exome AF: 0.151

Gnomad4 FIN exome AF: 0.156

Gnomad4 NFE exome AF: 0.0824

Gnomad4 OTH exome AF: 0.0879

GnomAD4 genome AF: 0.0897 AC: 13650 AN: 152168 Hom.: 951 Cov.: 32 AF XY: 0.0968 AC XY: 7205 AN XY: 74394

Gnomad4 AFR AF: 0.0326

Gnomad4 AMR AF: 0.102

Gnomad4 ASJ AF: 0.0418

Gnomad4 EAS AF: 0.356

Gnomad4 SAS AF: 0.185

Gnomad4 FIN AF: 0.176

Gnomad4 NFE AF: 0.0848

Gnomad4 OTH AF: 0.0795

Alfa AF: 0.0751 Hom.: 68

Bravo AF: 0.0812

Asia WGS AF: 0.219 AC: 763 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.023
DANN	Benign	0.30

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs6668814; hg19: chr1-111785126;